A subject of the present invention is a monoclonal antibody directed against aurora-A kinase of mammals, method for its obtention, as well as its uses in the context of the diagnosis or prognosis of cancers, and in pharmaceutical compositions for the treatment of cancers.
The aurora-A protein kinase is an oncogene, its overexpression in Rat-1 cells is sufficient to cause the appearance of a transformed phenotype and the implantation of these transformed cells into immunodeficient mice causes tumours to appear. (Bischoff et al., 1998; Zhou et al., 1998). The gene coding for this kinase is localized on the chromosome 20 at 20q13, amplicon frequently detected in numerous tumours (breast, colon, stomach cancers).
The overexpression of the aurora-A protein kinase has been observed in numerous tumours. Interestingly, the presence of this kinase in an abnormal quantity is not correlated to a proliferation detected by staining with a specific proliferation marker such as PCNA. Aurora-A is therefore a specific marker of the tumoral aspect of the cells (Tanaka et al., 1999; Takahashi et al., 2000).
Aurora-A belongs to a multigenic family of protein kinases called aurora, it comprises three members: aurora-A (described previously) aurora-B (Prigent et al., 1999) and aurora-C (Bernard et al., 1998). Although only aurora-A has a real oncogenic power the two other kinases have also been found overexpressed in the same tumours (Giet and Prigent, 1999).
The amplification of the gene coding for aurora-A is associated with the presence of an abnormally high activity of the protein kinase in these tumours. Moreover the ectopic overexpression of this kinase in cells in culture is sufficient to cause a transformed phenotype to appear, these cells transplanted into immunodeficient mice cause tumours to appear.
The overexpression of aurora-A kinase is very closely linked to the cancerous state of a cell. This overexpression of aurora-A kinase induces a polyploidy of the cells and causes an amplification of the centrosomes, two events which precede a poor prognosis for breast cancer for example.
It is therefore important to be able to precisely measure the expression of this kinase in cancerous pathologies, both at the level of the mRNA and the protein.
Now, the measurement of the expression of the aurora-A protein kinase depends entirely on the use of a good monoclonal antibody.
However, no sufficiently specific monoclonal antibody directed against the aurora-A protein kinase was able to be obtained until now, or is available commercially.